Zellweger spectrum disorders (ZSD) are rare autosomal recessive disorders caused by defects in peroxisome biogenesis factor (PEX; peroxin) genes leading to impaired transport of peroxisomal proteins with peroxisomal targeting signals (PTS). Four patients, including a pair of homozygotic twins, diagnosed as ZSD by genetic study with different clinical presentations and outcomes as well as various novel mutations are described here. A total of 3 novel mutations, including a nonsense, a frameshift, and a splicing mutation, in PEX1 from ZSD patients were identified and unequivocally confirmed that the p.Ile989Thr mutant PEX1 exhibited temperature-sensitive characteristics and is associated with milder ZSD. The nature of the p.Ile989Thr mutant exhibited different characteristics from that of the other previously identified temperature-sensitive p.Gly843Asp PEX1 mutant. Transcriptome profiles under nonpermissive vs. permissive conditions were explored to facilitate the understanding of p.Ile989Thr mutant PEX1. Further investigation of molecular mechanisms may help to clarify potential genetic causes that could modify the clinical presentation of ZSD.
X-linked adrenoleukodystrophy is caused by a defective peroxisomal membrane transporter, ABCD1, responsible for transporting very-long-chain fatty acid substrate into peroxisomes for degradation. The main biochemical defect, which is also one of the major diagnostic hallmarks, of X-linked adrenoleukodystrophy is the accumulation of saturated very-long-chain fatty acids in all tissues and body fluids.
Out-of-pocket (OOP) payments are the principal means of financing health care throughout much of Asia. We estimate the magnitude and distribution of OOP payments for health care in fourteen countries and territories accounting for 81% of the Asian population. We focus on payments that are catastrophic, in the sense of severely disrupting household living standards, and approximate such payments by those absorbing a large fraction of household resources. Bangladesh, China, India, Nepal and Vietnam rely most heavily on OOP financing and have the highest incidence of catastrophic payments. Sri Lanka, Thailand and Malaysia stand out as low to middle income countries that have constrained both the OOP share of health financing and the catastrophic impact of direct payments. In most low/middle-income countries, the better-off are more likely to spend a large fraction of total household resources on health care. This may reflect the inability of the poorest of the poor to divert resources from other basic needs and possibly the protection of the poor from user charges offered in some countries. But in China, Kyrgyz and Vietnam, where there are no exemptions of the poor from charges, they are as, or even more, likely to incur catastrophic payments.